Fascin is involved in cancer cell invasion and is regulated by stromal factors

Abstract

The tumor microenvironment plays an important role in cancer growth, invasion and metastasis. The stroma surrounding a tumor is known to contain a variety of factors that can increase angiogenesis, cancer growth and tumor progression. The aim of the present study was to determine the role of fascin in cancer growth and invasion and identify stromal factors involved in cancer progression. A fascin‑depleted cell line (fascindep) was used to observe the role of fascin in cancer invasion. Compared with wild‑type Mock cells, cancer cell invasion in Matrigel‑coated Transwell and three‑dimensional (3D) culture system were reduced by fascin depletion. Tumor cell growth in vivo was also significantly reduced in mice injected with fascindep cells. Notably, fascin expression was increased during Transwell invasion with Matrigel compared to Transwell invasion without Matrigel. TGF‑β1, EGF and IL‑1β significantly stimulated fascin expression. Such increased expression of fascin was also observed in cultured cells using conditioned media (CM) from cancer‑associated fibroblasts (CAFs). However, no significant change in fascin expression was observed using CM from normal fibroblasts (NFs). Stimulated expression of fascin by Matrigel and CAFs was reduced by biological specific inhibitor of TGF‑β1, EGF and IL‑1β. Compared with wild‑type Mock cells, the fascindep cell line showed low RhoA and NF‑κB activity, suggesting that RhoA and NF‑κB signals are involved in fascin expression. In conclusion, stromal factors are involved in cancer invasion and progression by activating intracellular signaling of cancer cells to increase fascin expression.